Lipoic Acid: A Promising Alternative Therapy for Alzheimer’s Disease

Lipoic acid: a promising alternative therapy for Alzheimer’s disease

This is the fourth In a series on complementary and alternative and integrative treatments of dementia. Previous posts reviewed the evidence for dietary changes, multi-modal interventions and a promising natural product called Huperzine derived from Chinese herbal medicine. This post is offered as a concise review of lipoic acid (also called alpha lipoic acid) a naturally occurring molecule in humans and many animals that plays essential roles in metabolism. Lipoic acid is found in red meat, broccoli, tomatoes, spinach and Brussels sprouts. It is used for weight loss and is widely prescribed in some European countries to treat diabetes, including a painful complication called diabetic neuropathy. LA is generally safe even when taken at high doses (2 to 3 grams per day) and may cause mild nausea, itching or rash. Absorption is best when taken on an empty stomach, 30 to 60 minutes before eating or a few hours after eating.

Promising but preliminary findings but few human studies

Findings from animal studies suggest that lipoic acid may slow the rate of cognitive deterioration in the early stages of Alzheimer’s disease. Beneficial effects are mediated by several mechanisms including increasing synthesis of acetylcholine, an important neurotransmitter required for the formation of new memories; increasing the activity of enzymes needed to synthesize glutathione, an important antioxidant; and savaging free radicals thus reducing inflammation in the brain that may increase the risk of developing Alzheimer’s disease (Maczurek et al 2008).

Few human clinical trials have been done on lipoic acid (LA) in individuals diagnosed with Alzheimer’s disease but most published findings are positive. In a small open pilot study 9 patients with probable AD were treated with lipoic acid 600mg daily for one year while taking cholinesterase inhibitors. All patients experienced stabilization in cognitive functioning which had previously been declining at a steady rate (Hager et al 2001). That open study was extended to 48 months and enlarged to include 43 patients diagnosed with mild Alzheimer’s disease, all of whom experienced significant slowing in the rate of cognitive deterioration during the study period (Hager et al 2007). Although promising, the significance of the above findings is limited by the absence of a placebo control arm and small study size, hence they should be regarded as preliminary pending confirmation by a large double-blind placebo-controlled trial.

Combining lipoic acid with other natural substances may be more effective than any single nutraceutical 

In addition to research on lipoic acid only, studies have investigated nutraceutical formulas that include LA in combination with other natural products known to have beneficial antioxidant or neuroprotective properties. An epidemiologic study found that individuals who regularly consume fruits and vegetables rich in polyphenols have a significantly reduced risk of developing Alzheimer’s disease (Dai et al 2006). Polyphenols are often recommended by health care providers because of their established protective effects against cancer and cardiovascular disease. Along similar lines, elderly individuals who frequently consume curry (which contains the antioxidant curcumin) or foods rich in the omega-3 fatty acid DHA, may have a significantly decreased risk of Alzheimer’s disease (Ng et al 2006; Morris et al 2003; Tully et al 2003). Curcumin is a more potent free radical scavenger than vitamin E and may inhibit build-up of amyloid beta plaque, one of the main causes of Alzheimer’s disease (Zhao 1989; Yang et al 2005). Mice that were genetically modified (i.e., transgenic mice) to develop Alzheimer’s disease were found to have significantly reduced amyloid levels after 6 months on a high curcumin diet (Yang et al 2005). Epigallocatechin gallate (EGCG), a molecule that occurs naturally in green tea, is another nutraceutical that has attracted recent attention because it prevents neuronal cell death caused by amyloid beta neurotoxicity in cell cultures and transgenic mice (Choi et al 2001; Rezai-Zadeh 2005). Findings of recent animal studies suggest that the omega-3 fatty acid DHA may help prevent AD by reducing amyloid beta accumulation thus decreasing the neurotoxic effects of amyloid beta (Florent 2006; Hashimoto 2005).

Human studies on combination treatments are needed

As the above nutraceuticals prevent or delay progression of Alzheimer’s disease via different mechanisms, combining them into a single formula might be more effective than any nutraceutical alone. In fact, findings of a recent animal study bear this out. In a just-published study, transgenic mice predisposed to develop Alzheimer’s disease treated with a combination of lipoic acid, curcumin and the omega-3 fatty acid DHA were found to have greater anti-inflammatory and neuroprotective effects compared to mice receiving only one nutraceutical (Sharman et al 2019). A large placebo-controlled trial in humans diagnosed with Alzheimer’s disease is needed to determine whether combining multiple nutraceuticals is more effective than single nutraceuticals. This is the domain of so-called multi-modal interventions, which I discussed in a previous post.

You can read more about complementary and alternative treatments of Alzheimer’s disease and mild cognitive impairment in my book “Dementia and Mild Cognitive Impairment: The Integrative Mental Health Solution.”

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For Alzheimer’s Disease Limitations of Conventional Treatment Invite Complementary and Alternative Therapies

This is the second post in a series on complementary and alternative treatments of dementia. The previous post examined the evidence for diet in reducing the risk of developing Alzheimer’s disease. This post begins with a short review of the limitations of available pharmacologic treatments then reviews findings on multi-modal approaches aimed at reducing inflammation and metabolic risk factors known to increase risk of Alzheimer’s disease, and optimizing lifestyle factors known to reduce risk.

Limitations of pharmacologic treatments

Currently available pharmacologic treatments of AD work by inhibiting the enzyme that breaks down acetylcholine, increasing available levels of the neurotransmitter that is critical for learning and memory. Promising early results of studies on tacrine, the first commercially marketed acetylcholinesterase inhibitor, were offset by findings of significant hepatotoxicity. Second-generation acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are no more effective than tacrine but require less frequent dosing and have fewer associated safety issues. These concerns led to discontinuation of tacrine in 2013.

Other medications that have been investigated for possible cognitive-enhancing benefits in dementia include the monoamine oxidase inhibitors (MAOIs), estrogen replacement therapy (i.e., in cognitively impaired postmenopausal women), naloxone, and various neuropeptides, including vasopressin and somatostatin (Zandi et al., 2005). Promising novel Western biomedical treatments of Alzheimer’s disease currently being investigated in clinical trials include a vaccine that may immunize individuals against formation of amyloid beta, secretase inhibitors, anti-inflammatory agents, and statins (Herline 2018; Cao 2018). Results of studies on statins in dementia have been inconsistent. However, a 2018 meta-analysis of 31 studies that met inclusion criteria for size and rigor found that regular statin use is associated with significant reduction of risk of developing dementia (Zhang 2018).

Multi-modal interventions aimed at optimizing life-style factors

Positive findings of studies on a preventive role of diet in dementia are confounded by the fact that individuals with healthy dietary habits also engage in other behaviors that reduce Alzheimer’s risk, for example, by exercising regularly and moderating alcohol consumption (Barberger-Gateau, Letenneur, Deschamps, Peres, Dartigues, & Renaud, 2002). These findings have led to studies on interventions that optimize lifestyle factors with the goal of preventing Alzheimer’s disease or slowing its rate of progression.

One third of Alzheimer’s disease cases are probably caused by modifiable lifestyle factors suggesting that multi-modal interventions addressing many factors may have important preventive benefits. Modifiable lifestyle factors include low education, hypertension, diabetes, obesity, smoking, sedentary lifestyle and depressed mood. Only one large multi-center study has investigated multi-modal interventions aimed at preventing Alzheimer’s disease in elderly at-risk individuals (Ngandu 2015). The authors found significant improvements in overall cognition, processing speed and executive functioning in the treatment group that were significantly greater than in the control group.

Recent case reports have been published of dramatic improvement in individuals diagnosed with early Alzheimer’s disease who adhere to multi-modal life style changes (Bredesen 2014) aimed at enhancing cognitive performance and reducing metabolic risk factors associated with inflammation. These findings show that, in at least some cases, symptoms of early Alzheimer’s disease can be reversed within 6 months after initiating a comprehensive lifestyle regimen (Bredesen 2014). The goal of this approach is to normalize multiple metabolic parameters related to inflammation in the body, thus interrupting the pathological processes that eventually lead to Alzheimer’s disease. The protocol, called metabolic enhancement for neurodegeneration (MEND), entails comprehensive laboratory screening that may include serologic studies of inflammatory markers, functional brain scans, genetic analysis of risk, and cognitive testing. Personalized lifestyle changes and nutritional strategies are subsequently recommended to correct underlying causal factors of cognitive decline identified in screening. Many individuals with early Alzheimer’s disease (including some individuals with the ApoE4 gene who are at very high risk of developing an early severe form of Alzheimer’s disease) who adhere to the MEND protocol report sustained improvement in cognitive performance for several years and no longer meet criteria for a diagnosis of Alzheimer’s disease. Large prospective controlled trials are needed to confirm these dramatic findings, elucidate the relative contributions of different lifestyle changes and metabolic factors to clinical improvement.

Bottom line

Most available pharmacologic treatments of Alzheimer’s disease are limited in efficacy however statins may significantly reduce risk. Preliminary research findings suggest that multi-modal interventions aimed at reducing inflammation including changes in diet, regular exercise, aggressive management of health problems such as hypertension and diabetes, and normalizing metabolic factors associated with increased Alzheimer’s risk, may significantly reduce the risk of developing Alzheimer’s disease, delay its onset or slow its rate of progression. Long-term prospective studies are needed to confirm these findings and elucidate the relative contributions of changes in specific lifestyle factors to reduced Alzheimer’s risk.

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Taking Care of Depressed Mood in Pregnancy Without Drugs

Following a brief review of the consequences of untreated depressed mood and risks associated with antidepressant use during pregnancy, I comment on the evidence for complementary and alternative (CAM) modalities widely used to treat this serious problem.

Consequences of depressed mood and antidepressant treatment for the mother, fetus, and child

As many as 25% of women become depressed during pregnancy and relatively few receive adequate care resulting in potentially serious adverse outcomes for the mother, fetus, and child (Grote et al 2010). Depressed mood during pregnancy is associated with poor prenatal care including not taking prenatal vitamins and prescription medications and increased rates of alcohol and illicit substance abuse all of which can have negative health consequences for the mother and the fetus. Of great concern, the depressed mood in the perinatal period significantly increases the risk of maternal suicide.

Perinatal depression increases the risk of pre-term birth and low birth weight, both of which increase the risk of health problems in the newborn and long-term developmental problems. Infants of depressed mothers are more irritable, have more sleep problems, are at increased risk of delayed motor and cognitive development (Hanley and Ovelander 2012).

Both depressed mood and antidepressant use during pregnancy are associated with increased risk of medical problems in the fetus and, subsequently, behavioral problems in the child (Yonkers 2014). Both depressed mood in the mother and fetal exposure to antidepressants may increase the risk of having a miscarriage (Anderson et al 2014). A meta-analysis of seven studies found that fetal exposure to an SSRI in the third trimester (but not in early pregnancy) was associated with significantly increased risk of medical and behavioral complications in the newborn including respiratory distress, seizures, neurologic disorders, irritability, and problems nursing (Grigoriadis et al 2014). Antidepressant use in pregnancy may increase the risk of pre-eclampsia however findings are confounded by the increased rate of pre-eclampsia in depressed women who do not take antidepressants (Palmsten et al 2013).

Complementary and alternative approaches

Because of risks associated with antidepressants many pregnant women who are depressed prefer to use complementary and alternative (CAM) approaches. A recent review of CAM modalities widely used to treat depressed mood in pregnancy found some evidence for omega-3s, folate, and vitamin D, regular physical activity and yoga, but insufficient evidence for recommending S-adenosylmethionine, selenium, zinc, magnesium, and the B vitamins riboflavin, pyridoxine and cobalamin (Reza et al 2018).

The balance of this post is a concise review of the evidence for CAM modalities commonly used to treat depressed mood during pregnancy.

Natural supplements

St. John’s wort (Hypericum perforatum) is widely used to treat depressed mood however the herbal may not be safe when taken during pregnancy because it interacts with several medications resulting in potentially negative health consequences. Many studies have established the antidepressant benefits of omega-3 essential fatty acids however studies on omega-3s in pregnant women report mixed findings. During pregnancy adequate dietary folate is essential for normal development of the fetal nervous system and pregnant women are advised to take folic acid daily. (Beydoun et al 2010). Daily folic acid supplementation may reduce the risk of depressed mood in pregnancy. Pregnant women with higher vitamin D levels are at reduced risk of depressed mood however findings of placebo-controlled studies are mixed (Spedding 2014; Gowda et al 2015). Although prenatal vitamins contain 400 IUs of vitamin D, a daily dose of 2000 IU may be needed to reach serum levels believed to be effective against depressed mood (Holick et al 2011). There is some evidence for antidepressant effects of selenium, zinc, and riboflavin however most studies are small and findings of placebo-controlled studies are inconsistent.

Other CAM modalities

Some depressed pregnant women who receive one hour of early morning full spectrum bright light exposure daily for at least three weeks reported significant improvements in mood however not all women respond to bright light therapy. Few studies have been done on acupuncture as a treatment of depressed mood during pregnancy and findings are mixed. Regular physical activity has established mood enhancing effects however only a few studies have been done on exercise for depressed mood in pregnancy and findings are mixed. Regular massage may have significant mood-enhancing effects and may also reduce the risk of premature birth. Regular yoga practice may reduce the severity of depressed mood in some cases but findings are inconsistent.

Bottom line

Because of the safety risks associated with antidepressant use during pregnancy many women are exploring a range of CAM modalities however for the most part research findings are mixed. The most appropriate treatment strategy for depressed mood during pregnancy depends on the severity of depressed mood, safety considerations for both the mother and the unborn fetus, and patient preferences. Depending on the unique factors in each case, the most prudent treatment regimen may include an antidepressant, one or more natural supplements, bright light exposure therapy, exercise, yoga, or a combination of modalities.

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A Chinese Herbal Extract that Holds Promise Against Alzheimer’s Disease

Limitations of mainstream treatments of Alzheimer’s disease

Available prescription medications used to treat Alzheimer’s disease (AD) may temporarily lessen the severity of memory loss and other cognitive and behavioral symptoms associated with AD, but they do not correct its root causes nor do they reverse the steady cognitive decline typical of dementia (Dou et al 2018). The cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) often cause vomiting, nausea, appetite loss and diarrhea. Early promising results of studies on tacrine, the first commercially marketed acetylcholinesterase inhibitor, were offset by findings of significant hepatotoxicity. Second-generation acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are no more effective than tacrine but require less frequent dosing and have fewer associated safety issues. These concerns led to the discontinuation of tacrine in 2013. In contrast to the cholinesterase inhibitors, Memantine acts by antagonizing glutamate neurotransmitter receptors. A combined regimen of donepezil and memantine is sometimes used to treat severe symptoms of AD (Dou et al 2018).

Huperzine A: what it is and how it works

Huperzine A is an alkaloid derivative of the herb Huperzia serrata and is an important ingredient of many compound herbal formulas used in Chinese medicine to treat cognitive impairment related to normal aging. Huperzine A reversibly inhibits acetylcholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine which plays a critical role in the formation of new memories. Huperzine may also slow the production of nitric oxide in the brain, reducing age-related neurotoxicity (Zhao & Li, 2002).

Research review

Findings on Huperzine A for AD are inconsistent. An early human trial reported that Huperzine A may be more effective than piracetam for age-related memory loss (Wang et al., 1994). Several early placebo-controlled trials reported consistent beneficial effects in both age-related memory loss (i.e., benign senescent forgetfulness) and Alzheimer’s disease at doses between 0.2 and 0.8 milligrams per day (Wang et al. 1994). However, findings of recent systematic reviews remain inconclusive.

Two systematic reviews of placebo-controlled randomized trials on Huperzine A in patients diagnosed with Alzheimer’s disease (AD) found inconclusive evidence that Huperzine A ameliorates symptoms of memory loss and other cognitive problems. Methodological problems and small study size were cited as issues in both reviews (Li et al 2008; Li-Min and Ju-Tzu 2011). A 2013 systematic review (Yang et al 2013) included 10 randomized controlled trials found evidence for improved cognitive function as measured by the MMSE and other standardized rating scales but reported inconclusive evidence for Huperzine A in AD based on heterogeneity in study designs (different durations, different dosing protocols, different measures of cognitive performance), poor methodological quality of many studies (e.g., unclear blinding, unreported dropout rates during trial, randomization protocols not reported), short study duration (most studies were 8 or 12 weeks long) and small study size. Because most studies on Huperzine A are of short duration, it is possible that observed beneficial effects might reflect temporary symptomatic improvement (Tian et al 2010). However, as most studies do not report adverse effects thus the reviewers could not comment on its safety profile.

Few safety issues

Huperzine A is generally well tolerated (Rafii et al 2011). Huperzine A is generally safe when used at dosages indicated for AD and other cognitive problems. As the molecule functions in the same way that pharmaceuticals work to improve memory, individuals who take it report similar adverse effects such as nausea, and diarrhea. However, they are less frequent and milder than reported with pharmaceutical cholinesterase inhibitors.

Bottom line

In the face of limitations of available pharmacologic treatments of Alzheimer’s disease Huperzine A, a component of a traditionally used herbal in Chinese medicine, is a promising alternative approach. Methodological problems in many studies make it difficult to draw definitive conclusions about its effectiveness, and findings should be viewed as preliminary pending confirmation by large well-designed studies.

To learn more about complementary and alternative treatments of dementia read my book Dementia and Mild Cognitive Impairment: The Integrative Mental Health Solution.

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Low Fat Diets Significantly Reduce Risk of Dementia

Diets low in saturated fat and total calories and moderate alcohol consumption reduce the risk of developing Alzheimer’s disease

Diet may be the most important preventable risk factor in Alzheimer’s disease. Foods that increase the risk of Alzheimer’s include red meat, foods with high sugar content, and high-fat dairy products. Individuals who consume a high-fat, high-calorie diet are at significantly greater risk of developing Alzheimer’s dementia compared with individuals who have moderate fat intake and restrict total calories. High red meat consumption also impacts health in general by increasing the risk of several types of cancer, diabetes, obesity, kidney disease and stroke.

A meta-analysis of findings from 18 community-wide studies concluded that the risk of Alzheimer’s disease increased linearly at a rate of 0.3% with every 100-calorie increase in daily intake (Grant, 1997). Average daily fat consumption was highly correlated with increased risk of developing dementia. The same meta-analysis showed that fish consumption was the only specific dietary factor associated with a measurable reduction in the risk of developing Alzheimer’s disease.

The relationship between diet and Alzheimer’s risk is complex and probably involves oxidative stress caused by red meat, atherosclerosis caused by high cholesterol, and formation of damaging molecules caused by dysregulation of insulin secretion. High caloric intake and high fat intake promote formation of damaging free radicals that cause diffuse neuropathological changes in the brain, eventually manifesting as Alzheimer’s disease.

Established preventive benefits of the Mediterranean diet

Foods known to reduce the risk of developing Alzheimer’s disease include vegetables, grains, fish and fruits. Individuals who consume a traditional Mediterranean diet are at roughly one half the risk of developing Alzheimer’s disease compared to individuals who consumer a high-fat high-calorie diet, and individuals in countries with very low meat consumption such as Japan, are at even lower risk of developing Alzheimer’s disease (Grant 2016). Fish are an important source of omega-3 fatty acids, for which there is emerging evidence of beneficial and possibly preventive effects in dementia and less severe forms of cognitive impairment.

Heavy chronic drinking increases dementia risk while moderate drinking reduces risk

Heavy chronic alcohol abuse increases the risk of vascular dementia caused by stroke however moderate alcohol consumption (2–4 glasses of wine per day) is associated with reduced risk of Alzheimer’s disease (Orgogozo et al., 1997; Letenneur 2004).

Dietary changes are an important preventive strategy

Recent research findings show that changes in the brain associated with increased risk of developing Alzheimer’s disease start many years before the onset of cognitive decline. Thus proactive dietary changes represent an important strategy for delaying or preventing Alzheimer’s disease (Rodriguez-Vieitez 2016).

Take home lessons

Red meat and high calorie foods significantly increase the risk of developing Alzheimer’s disease, many kinds of cancer, diabetes and other serious medical problems. A Mediterranean diet and moderate alcohol consumption reduce Alzheimer’s risk. In response to the growing body of evidence for the central role of diet in Alzheimer’s disease risk, the Physicians Committee for Responsible Medicine has recommended minimizing intake of saturated fats and trans fats and replacing meats and dairy products with fresh vegetables, fruits, and whole grains (Barnard 2014).  Finally, widespread red meat consumption is correlated with increased global warming because of the relationship between large scale cattle production and methane being released into the atmosphere, thus reducing meat consumption may be an important factor in slowing the rate of global warming.

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Niacin, Thiamin, Vitamin C, Magnesium and Zinc May Reduce Alcohol Toxicity

This post is the sixth in a series on non-pharmacologic approaches for managing symptoms related to alcohol and drug abuse and withdrawal and decreasing the risk of relapse. Previous posts commented on evidence for natural supplements, weak electrical current and mindfulness for reducing drug and alcohol use and treating symptoms of withdrawal. This post is offered as a concise review of the evidence for certain B-vitamins, vitamin C, magnesium and zinc for reducing alcohol craving.

Chronic drinking leads to deficiencies in several B vitamins

Chronic drinkers are often deficient in several B vitamins including thiamin, folate, B-6 and B-12 because of toxic effects of alcohol on the mucosal lining of the stomach and small intestine that interfere with normal absorption. The conventional Western medical treatment of Wernicke’s encephalopathy, a condition of acute confusion and delirium sometimes seen in chronic heavy alcohol abuse, is intravenous administration of thiamin followed by oral thiamin supplementation 500mg per day.

Some B-vitamins and Vitamin C may decrease craving, increase alcohol clearance from the blood and reduce the severity of hangovers

Animal studies suggest that low serum thiamin levels are associated with increased alcohol craving (Zimatkin 1996). There is evidence that the B vitamin niacin in the form of nicotinamide dosed at 1.25 grams taken with a meal before drinking may protect the liver against the acute toxic effects of alcohol in individuals who have relapsed or are unable to abstain (Volpi 1997). Niacin in the form of nicotinic acid may reduce the risk of developing alcohol dependence by interfering with the synthesis of a morphine-like substance that is formed when acetaldehyde—a metabolite of alcohol—condenses with dopamine (Davis 1970).

For individuals who are unable to stop drinking, taking anti-oxidant vitamins close to the time of alcohol consumption may reduce or prevent hangover symptoms by neutralizing metabolites of alcohol that cause oxidative damage to the body and brain (Altura 1999; Marotta 2001). Findings of a small open study that enrolled 13 healthy males suggest that taking vitamin C before drinking may increase the rate at which alcohol is cleared from the blood. Taking 2 grams of vitamin C one hour before alcohol consumption increases the rate at which alcohol is cleared from the blood, and may reduce acute toxic effects on the liver (Chen 1990). This significance of this finding is limited by small study size and the absence of blinding and a control group.

Magnesium and zinc supplementation may improve neuropsychological deficits caused by chronic drinking

Magnesium supplementation 500 to 1500mg per day, may improve cognitive deficits associated with chronic alcohol abuse by improving cerebral blood flow which is often diminished in chronic alcoholics (Thomson 1988). Deficiencies in Zinc, copper, manganese and iron are common in alcoholics and worsen with continued heavy use. The diffuse nerve cell damage that is frequently associated with chronic alcohol use is probably caused by low serum Zinc levels which promote increased formation of damaging free radicals (Menzano 1994).

Bottom line

Most research findings on B vitamins, vitamin C, and other supplements for reducing drinking, controlling craving, and mitigating the toxic effects of alcohol on the body and brain come from small studies done many years ago that have not been replicated by large placebo-controlled studies. Despite the paucity of evidence for these supplements, select B vitamins and vitamin C have well established general beneficial effects at many levels of the body and brain, have no associated risks, and may mitigate the toxic effects of alcohol abuse in some cases.

Anyone who is struggling with a serious drinking problem should seek professional care. However, heavy drinkers who are unable to stop drinking or moderate drinking behavior, may benefit from supplementation with select B vitamins, vitamin C, magnesium and zinc because of their neuroprotective and antioxidant effects on the body and brain.

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Meditation and Mindfulness Practice Reduce the Risk of Relapse

This is the fifth post in a series on non-pharmacologic approaches for alcohol and drug abuse. Previous posts reviewed the evidence for weak electrical current for managing withdrawal symptoms and herbals and other natural supplements for managing craving and withdrawal from alcohol and drugs. This post is offered as a concise review of the evidence for mindfulness training for relapse prevention.

Mindfulness training and meditation reduces alcohol and drug relapse risk

Many studies show that regular mindfulness training can modify these neural mechanisms resulting in decreased substance use and lower risk of relapsing. Research findings suggest that substance abuse is related to abnormal functioning of brain mechanisms underlying reward learning and executive functioning (Priddy 2018).

Individuals who successfully avoid relapse while participating in a 12-step program frequently experience increases in spirituality (Mathew 1996). Mindfulness training and meditation are standard offerings in relapse prevention programs. Transcendental meditation may be especially effective in reducing the risk of relapse in abstinent alcoholics (Alexander 1994). Mindfulness training and spirituality are important parts of 12-step programs for relapse prevention of alcohol, tobacco and narcotic abuse, however evidence does not support any particular spiritual or mindfulness practice over any other. 12-step programs that emphasize a religious or spiritual philosophy may be more effective compared to spiritually neutral programs (Muffler 1995) (Please see full citation information below).

Two recent systematic reviews concluded that mindfulness-based interventions were successful for reducing use of several substances of abuse including alcohol, methamphetamine, cocaine, alcohol, marijuana, cigarettes and opiates while often improving mood (Sancho 2018; Chiesa 2014). The paper by Sancho et al found that individuals who engage in regular mindfulness practice while receiving treatment as usual (i.e., cognitive behavioral therapy (CBT) and medication management), report lower relapse rates compared to individuals using mindfulness or conventional approaches alone.

Bottom line

There is considerable evidence that a regular mindfulness practice helps individuals with substance use problems to use less, and reduces the risk of relapse in abstinent individuals. Recovering alcoholics and addicts should be encouraged to pursue a mindfulness practice consistent with their beliefs and to consider attending a spiritually focused support group that combines conventional approaches such as cognitive-behavioral therapy with mindfulness.

To find out more about non-pharmacologic approaches for relapse prevention check out my book “Alcohol and Drug Abuse: The Integrative Mental Health Solution.”

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Natural Supplements for Treating Alcohol and Drug Abuse and Withdrawal: A Concise Review

This is the fourth installment in a series of posts on non-pharmacologic approaches to alcohol and drug abuse. Previous posts reviewed the evidence for weak electrical current for reducing symptoms of opioid and alcohol withdrawal. This post is offered as a concise review of promising herbal and other natural product treatments of alcohol craving and withdrawal, narcotic withdrawal and benzodiazepine withdrawal.

Traditionally used herbal medicines may reduce alcohol craving, lessen alcohol consumption and reduce symptoms of withdrawal

Three herbs are used in Chinese medicine to diminish alcohol craving, lessen alcohol absorption through the gut, or reduce symptoms of withdrawal. Kudzu (Radix puerariae) has been used as a treatment of alcohol abuse and dependence in Chinese medicine for almost 2000 years. Animal studies suggest that Kudzu extract significantly reduces alcohol craving (Keung 1993). A recent placebo-controlled human study found that individuals who had the opportunity to binge drink significantly reduced their drinking after taking 2gm of a standardized Kudzu extract 2 1/2 hours before starting to drink (Penetar 2015).

Salvia miltiorrhiza is a widely used herb in Chinese medicine that may reduce absorption of alcohol through the stomach. Animal studies suggest that S. miltiorrhiza reduces alcohol seeking behavior in rats genetically engineered to prefer alcohol. Blood alcohol levels were reduced by 60% in rats that had been pre-treated with S. miltiorrhiza. Aralia elata is a component of a compound Chinese herbal formula traditionally used to prevent or mitigate alcohol intoxication. Animal studies suggest that the herbal A. elata is a potent inhibitor of alcohol absorption (Yoshikawa 1996). Ibogaine is a naturally occurring alkaloid extracted from the root of an African shrub (Tabernanthe iboga). Preparations of the herb have been used as a stimulant in traditional African culture for centuries. Animal studies suggest that ibogaine and its primary metabolite, noribogaine, significantly reduce alcohol consumption in rats genetically engineered to prefer alcohol. Cannibis indica, an important Ayurvedic medicinal herb, may be an effective treatment for delirium tremens, a potentially fatal complication of acute alcohol withdrawal. Case reports from as early as the mid-19th century suggest that Cannibis indica provides rapid relief from symptoms of delirium tremens when administered orally in sequential doses over a 24-hour period (Godfrey 1996) (Please see full citation in references). The findings of an open trial suggest that Mentat, ™ a proprietary Ayurvedic compound herbal formula, may reduce the risk of relapse in abstinent alcoholics (Trivedi 1999). (Please see full citation in references)

Ashwagondha, Ginseng, and other natural products may reduce the severity of withdrawal from opiates, and reduce tolerance to cocaine, methamphetamine and morphine

Ashwagondha (Withania somnifera) is an important herb in traditional Ayurvedic medicine. Anecdotal reports and findings of animal studies suggest that Ashwagondha lessens the severity of withdrawal from morphine. Mice pre-treated with Ashwagondha for ten days did not develop tolerance to analgesic effects of morphine, suggesting that Ashwagondha may have similar beneficial effects in human heroin addicts (Ramarao et al, 1995; Kulkarni & Ninan, 1997). Ginseng (Panax ginseng) is widely used in both Chinese medicine and Western herbal medicine. Animal studies suggest that Ginseng may reduce tolerance and dependence associated with the long-term abuse of cocaine, methamphetamine or morphine. Repeated use of cocaine or methamphetamine results in chronically depleted dopamine. The mechanism of action responsible for reduced tolerance observed with Ginseng may involve inhibition of narcotic-induced depletion of dopamine in the brain.

Valerian extract and a proprietary Ayurvedic formula may reduce the severity of benzodiazepine withdrawal

Valerian (Valeriana officinalis) extract may lessen withdrawal symptoms and facilitate return to a normal sleep pattern following prolonged use of benzodiazepines such as clonazepam and lorazepam. The findings of animal studies show that Valerian in doses of 12mg per kilogram attenuates withdrawal symptoms in diazepam-dependent rats (Andreatini 1994). Mentat™, a proprietary Ayurvedic compound herbal formula, has been found to reverse effects of acute benzodiazepine withdrawal in dependent mice, and may provide similar benefits in humans (Kulkarni 1994; Kulkarni 1992).

Melatonin may help individuals discontinue benzodiazepines following prolonged use

Melatonin may facilitate discontinuation of benzodiazepines when there is dependence following chronic use. In a 12-week single-blind placebo-controlled study patients receiving controlled release melatonin 2mg/night were more likely to discontinue benzodiazepines compared to patients taking a placebo (Garfinkel 1999). Patients taking melatonin reported significantly greater improvements in subjective sleep quality compared to the placebo group. Most patients who continued to take controlled release melatonin at night remained off benzodiazepines six months after the end of the study. In view of these findings individuals who are attempting to taper and discontinue benzodiazepines following prolonged use for insomnia should be encouraged to take a nightly 2mg dose of controlled release melatonin. The above findings should be viewed in the context of a 2105 systematic review and meta-analysis that found no evidence that melatonin facilitated benzodiazepine discontinuation and inconsistent effects of melatonin on sleep quality (Wright 2015) .

Polyenylphosphatidylcholine (PCC) may reduce liver damage in chronic alcohol abuse

Polyenylphosphatidylcholine (PPC) is a natural product that is believed to reduce induction of liver enzymes associated with alcohol intake. Animal studies suggest that PPC reduces liver damage when taken before alcohol consumption (Lieber 1997; Aleynik 1999). HepatoPro ™ and other commercial products containing PPC are currently used before drinking in West European countries to protect the liver from damage.

Supplementation with fatty acids may reduce the severity of alcohol withdrawal, and improve mood and overall cognitive performance

Chronic alcohol use causes depletion of Omega-3 fatty acids and related molecules in nerve cell membranes, which in turn, may predispose alcoholics to depressed mood and other menta; health problems (Hibbeln 1995). In a small double-blind placebo-controlled trial supplementation with Omega-6 fatty acids in the form of Evening Primrose oil reduced the severity of withdrawal from alcohol, normalized liver enzymes, and significantly improved cognitive performance (Glen 1984). (Please see full citation in references).

Bottom line

Most studies on herbals and other natural supplements for reducing alcohol or drug use, reducing craving and managing withdrawal were small, conducted many years ago and have not been replicated by large placebo-controlled studies. Nevertheless, there is evidence that some herbal medicines widely used in Chinese medicine, Ayurveda (the system of medicine used in India) may significantly reduce craving and consumption of alcohol and may reduce the severity of alcohol withdrawal. A natural product called polyenylphosphatidylcholine may reduce liver damage in chronic alcohol abuse and fatty acid supplementation may reduce the severity of alcohol withdrawal while improving mood and overall cognitive performance. There is also evidence that the herbals ashwagondha, Ginseng, and select other natural products may reduce the severity of withdrawal from opiates, and reduce tolerance to cocaine, methamphetamine and morphine. Valerian extract and a proprietary Ayurvedic formula may reduce the severity of benzodiazepine withdrawal however, melatonin is probably not effective for facilitating discontinuation of benzodiazepines or improving sleep quality following chronic use.

If you are struggling with an alcohol or drug abuse problem it is prudent to consult with a mental health provider or an addiction specialist before considering any natural product supplement. 

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Weak Electrical Current May Reduce Symptoms of Alcohol and Cocaine Withdrawal

Cranioelectrotherapy stimulation (CES) for alcohol and cocaine abuse and withdrawal

Numerous studies dating back to the 1970s have investigated the efficacy of weak electrical currents in the treatment a variety of mental health problems including anxiety disorders, depressed mood, insomnia and alcohol and drug abuse. Depending on the technique used, these therapies are described as cranioelectrotherapy stimulation (CES) transcranial electrical stimulation (TES). TES is widely used in Germany and other countries in the European Union for the management of alcohol and narcotic withdrawal. CES has been approved by the U.S. Food and Drug Administration (F.D.A.) as a treatment of chronic pain syndromes and anxiety and is widely used to treat both conditions. In my previous post I reviewed evidence for cranioelectrotherapy stimulation (CES) for reducing symptoms of opiate withdrawal. In this post I take a brief look at studies on CES for treating symptoms of alcohol withdrawal.

Review of research findings

In a 7-year prospective study of CES in the treatment of alcohol, drug and nicotine addiction, acute and chronic withdrawal symptoms were diminished, normal sleep patterns were restored more rapidly and more patients remained addiction-free following regular CES treatments compared to conventional psychopharmacological management. CES-treated patients had significantly fewer anxiety symptoms and higher quality of life measures compared to patients treated with prescription medications (Patterson 1984). Findings of several sham-controlled studies suggest that CES may significantly reduce the time needed for abstinent alcoholics and drug addicts to regain normal cognitive functioning following prolonged drug use or drinking (Smith 1982; Schmitt 1984). Regular CES treatments compare favorably with psychotherapy combined with relaxation training and biofeedback in reducing anxiety in patients abusing any substance (Overcash 1999).

In a 4-week double-blind study, 20 depressed alcoholics were randomized to receive 20 CES treatments at 70 to 80Hz, 4-7mA versus sham treatments. Patients who received CES treatments experienced significantly reduced anxiety by the end of the study. No adverse effects were reported (Krupitsky 1991). This finding suggests that CES might provide an effective non-pharmacological alternative treatment of anxiety in alcoholics while avoiding the risks of cross-tolerance and dependence associated with benzodiazepines. In contrast to established therapeutic benefits CES for managing symptoms of withdrawal from alcohol or opiates (my see my previous post), this approach does not facilitate smoking cessation or reduce nicotine withdrawal symptoms. A 5-day sham-controlled study randomized 51 smokers who were motivated to stop smoking to daily CES (30 microA, 2-msec, 10Hz pulsed signal) versus sham-CES (Pickworth 1997). At the end of the study there were no significant differences between CES and sham-CES in daily cigarettes smoked, smoking urges or nicotine withdrawal symptoms.

Infrequent mild adverse effects

A recently published review of safety issues associated with transcranial electrical stimulation found almost no adverse effects in over 18,000 sessions administered to healthy individuals, neurologic and psychiatric patients (Antal 2017). Infrequently reported transient adverse effects include mild tingling and burning sensations, headache and fatigue. The authors commented on 11 documented cases of possible mania induction in individuals diagnosed with depression however these cases could not be definitively linked to TES because of the small number of individuals enrolled in controlled trials.

Bottom line

There is evidence that regular CES treatments may reduce the severity of withdrawal and reduce time needed for return of normal cognitive functioning, restore normal sleep patterns, and reduce anxiety in the early stages of abstinence in individuals who abuse cocaine or alcohol. CES is widely used in rehabilitation centers and may provide an effective, affordable and practical alternative to conventional medication management of detoxification and withdrawal from alcohol, cocaine and heroin. However, CES does not reduce nicotine craving or withdrawal in individuals who are trying to stop smoking. I encourage you to find a therapist who is experienced in the use of CES if you are considering trying CES as part of a recovery program.

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Neuroelectric Therapy for Managing Opioid Withdrawal

Urgent need for improved management of opioid withdrawal

This is the second post in a series on non-medication approaches for alcohol and drug abuse. Opioid addiction is a public health crisis in the U.S. It is estimated that as many as 36 million Americans abuse prescription opioid pain medications and approximately 500,000 are addicted to heroin. Effectively managing withdrawal and detoxification is critical to successful discontinuation of heroin or prescription opioid pain medications. Individuals undergoing opioid detox are more likely to leave treatment prematurely when opioid withdrawal symptoms are not adequately managed. This post reviews research findings on neuroelectric therapy, an approach that employs weak electrical current to mitigate symptoms of opioid withdrawal. A future post will review the evidence for neuroelectric therapy in managing alcohol withdrawal.

How neuroelectric therapy works

The term neuroelectric therapy is used to describe Cranial electrotherapy stimulation (CES) and Transcranial neuroelectric stimulation (TES), two techniques that use weak electrical current to reduce symptoms of opiate withdrawal such as depressed mood, pain, agitation and insomnia. TES is widely used in Germany for the management of withdrawal symptoms. Both approaches involve the application of weak electrical current to specific points on the scalp or ears at regular intervals during acute withdrawal from opiates, alcohol or nicotine. CES typically uses a single frequency setting, 100Hz. In contrast, TES treatments use multiple pulse frequencies and wave forms to lessen symptoms of detoxification depending on the particular substance of abuse and the stage of withdrawal that is being managed. In contrast to conventional pharmacological approaches, micro-current stimulation offers the important advantage of avoiding the use of other potentially addictive narcotics when managing symptoms of opiate withdrawal.

The mechanism of action by which weak electrical current reduces symptoms of alcohol and opiate withdrawal involves stimulation of release of endogenous brain opioid peptides including endorphins, enkephalins and others, and may be similar to the biological mechanism underlying electro-acupuncture. A recent study suggests that weak electrical current may modulate the activity of the amygdala or other limbic brain regions reducing pain and unpleasant emotions frequently associated with opioid withdrawal (Miranda & Taca 2017).

Inconsistent research findings

After decades of research findings on the efficacy of neuroelectric therapy for managing opioid withdrawal are inconsistent.

While some studies report significant benefit, other studies report negative or equivocal findings. In one small, open retrospective pilot study, charts were reviewed for 73 adults who had been managed for acute opioid withdrawal using a non-invasive electrical nerve stimulator (Miranda & Taca 2017). Most patients reported rapid reduction in withdrawal symptoms following 20 minutes of treatment which were sustained on 5-day follow-up. Following treatment with the nerve stimulator the majority of patients were successfully transitioned to conventional medication assisted therapy.

The mechanism of action is believed to involve stimulation of the amygdala (or other limbic structures) resulting in lessening of both physical discomfort and dysphoria that frequently accompany opioid withdrawal. Findings of another small study suggest that individuals who receive micro-current stimulation and methadone have less severe withdrawal symptoms than individuals using methadone alone (Bakhshani 2008). A 2013 review of controlled and uncontrolled studies and case reports on neuro-electric therapy for found ‘generally poor’ evidence for this approach in reducing opioid withdrawal and craving (Lincolnshire Knowledge and Research Service 2013).

Bottom line: more research needed 

Neuroelectric therapy should be regarded as potentially efficacious but provisional non-medication therapy for managing opioid withdrawal. Inconsistent research findings may reflect methodological differences in study design, the small number of sham-controlled studies, small study sizes and the absence of standardized treatment protocols. Pending confirmation by large well-designed sham-controlled studies neuroelectric therapy may prove to be a practical and affordable non-medication treatment of opioid withdrawal.

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