The Role of Nutrition in Addiction Recovery: What We Know and What We Don’t

Introduction

The addiction epidemic in the United States has now reached crisis proportions. It is no longer a topic confined to healthcare professionals and is now receiving considerable attention by the press, media, and politicians. Recent data shows widespread use in adolescents and teens. With substance use disorder (SUD) rates rising, there is an urgent need for new and innovative treatment modalities. The concept of using nutrition to treat addiction was proposed as early as 1955 but has not yet been accepted in conventional SUD treatment. In 1990, the American Dietetic Association (now called the Academy of Nutrition and Dietetics) published a position paper declaring that nutrition intervention is an essential component of treatment and recovery from SUD. Unfortunately, the position statement was never implemented and there has been little progress incorporating nutrition professionals into treatment settings. At the present time, specialized training programs for nutritionists seeking work in addiction treatment settings do not exist. In the past decade, many private sector addiction treatment facilities have begun to incorporate “holistic” approaches to recovery, which include an emphasis on healthful eating, but there are no established standards of practice. Recently, nutrition therapy guidelines have been developed for specific intoxicating substances and this chapter will add to that body of knowledge by emphasizing the latest advances in our understanding of gastrointestinal (GI) health. This paper summarizes the impact of substances on nutritional status and proposes strategies that can be employed to replenish and improve eating behavior in treatment settings. Because drugs and food are both associated with cognitive control and executive functioning in risk/reward decision-making, intervention strategies are grounded in accepted concepts of neuroscience and psychology.

Dietary Patterns and Malnutrition. It is well established that individuals with severe SUD may have inadequate dietary intake leading to malnutrition. In a large sample of Canadian intravenous (IV) drug users, 65% met criteria for hunger, which was strongly correlated with depression, and 74% had inadequate housing. Preference for sweets and other easily digestible foods (i.e., refined cereal) and a low intake of fruits and vegetables is a consistent finding in street dwelling drug addicts. In one study of 140 heroin and cocaine addicts admitted to a hospital, 18% were considered severely malnourished (serum albumin under 3.5 g/dL and/or serum transferrin under 200 mg/dL), which was worse in females compared to males. These authors also found that the heaviest drug users were also the most malnourished. Research on HIV-infected heroin-addicted females has shown malnutrition in all subjects while using but are able to improve their nutritional status after 6 months of detoxification.

Micronutrient Imbalances. Micronutrient deficiencies have been observed in several studies of patients with SUD. Specifically, deficiencies in antioxidant vitamins E, C, and A have been reported. Studies have revealed iron deficiency and anemia. Elevated levels of serum copper and zinc are commonly seen in subjects with SUD indicative of infection and inflammation, slowly returning to normal after abstinence and nutrition intervention. It is possible that imbalances in serum trace minerals alter trace elemental concentrations in the brain which can lead to oxidative damage. Plasma nitric oxide metabolites are higher among persons with substance use disorder compared to controls, suggesting injury by free radicals and an oxidant–antioxidant disturbance that has been implicated in the pathomechanism of relapse.

Weight Concerns. Many persons with SUD report gaining weight during early recovery, although there is no established association between lifetime illicit drug abuse and BMI. Heavy injection drug users have a lower percent body fat than nondrug users. Hyperphagia has been linked to drug discontinuation as well as smoking cessation. In one study of adolescents in treatment, weight gain occurred independent of smoking and psychotropic medication use. Men in addiction treatment have described dysfunctional eating behaviors such as bingeing and using food to regulate mood in early recovery (1–6 months) as well as distress about efforts to lose weight in later recovery (7–36 months). Women who gain weight in early recovery have expressed interest in incorporating nutrition and exercise into their recovery program. In one study (n = 297), 43% of women expressed concern that weight gain could trigger drug relapse and other treatment research (n = 124) has shown that weight-related concerns exist in 70% of women. According to many authors, consideration should be given to prioritizing efforts to improve environmental supports for healthful eating within residential recovery programs.

Alcohol

Chronic Disease. Weight gain and obesity have been associated with an increased risk for lifetime alcohol use disorder (AUD) in men but not women. On the other hand, epidemiological studies support a link between familial alcoholism risk and obesity for women but less so for men. Recent data from a French study suggests that drinking frequency is positively associated with increased BMI and waist circumference independent of drinking patterns. In detoxified patients with AUD, there is evidence of abnormal blood pressure response to variations in salt intake that is similar to sodium-sensitive arterial hypertension, suggesting a possible susceptibility of alcohol abusers to cardiovascular disease (CVD). Other authors have suggested hyperhomocysteinemia may play a role in the development of CVD among patients with alcoholic liver disease (ALD). Investigators in Japan have suggested that ethanol-related colorectal cancer might be linked to the presence of anaerobic bacterial strains that accumulate acetaldehyde under aerobic conditions in the colon and rectum. The data strongly suggests that AUD leads to gut dysbiosis (a condition in which the symbiotic relationship between gut microbiota and host is lost) and peripheral inflammation.

Alcoholic Liver Disease. Recent advances in the assessment of the gut microbiome have changed our understanding of ALD. Evidence suggests that gut health may be linked to ALD by way of a gut-liver axis. Chronic alcohol consumption leads to higher synthesis of bile acids, which may explain the pathogenesis of colonic inflammation in ALD. A recent review summarized the importance of dietary lipids in the progression of ALD. Specifically, proinflammatory omega-6 fatty acids have demonstrated deleterious effects on liver injury in animal models. Additionally, the progression of ALD appears to be linked to the progression of lung disease by way of increased oxidative stress and activation of the inflammatory cascade.

Microbiome. It has been well established that excessive alcohol negatively impacts the microbiome leading to dysbiosis in humans and animals. Normal gut microbiota appears to be involved in inhibiting the growth of pathogenic bacteria in order to prevent conditions such as small intestinal bacterial overgrowth. Intestinal microbiota function is altered in AUD leading to increased markers of oxidative stress and decreases in the short-chain fatty acids (SCFAs), propionate and isobutyrate, which are important in maintaining intestinal epithelial cell health and barrier integrity.

Immune dysfunction in AUD may be related to a disruption in the integrity of the tight junction (intestinal barrier), allowing bacterial translocation into the portal vein or through gastrointestinal lymphatics. Lipopolysaccharide (LPS) is a major component of the outer wall of many Gram-negative bacteria which may allow translocation from the lumen of the intestine into the portal circulation and then travel to the liver. Gram-negative bacterial overgrowth results in augmented endotoxin levels that cause hepatic damage. Research has shown that gut “leakiness” and associated inflammation (measured by LPS, TNFα, IL-6, IL-10, and hsCRP) in noncirrhotic alcohol-dependent subjects correlate to measures of depression and alcohol craving. After 3 weeks of abstinence, alcohol-dependent subjects with gut leakiness had higher degrees of depression, anxiety, and craving than those with less gut permeability. These authors suggest that these psychological symptoms may contribute to a negative reinforcement process involved with persistence of AUD. Since not all subjects developed gut leakiness, chronic alcohol consumption by itself is not sufficient to cause gut dysfunction; therefore, other variables (e.g., diet, smoking, genetics, immune status) are likely involved. Other subjects with AUD displayed evidence of alcohol gut dysbiosis that persisted after an extended period of sobriety and in the absence of ALD. A recent review summarized the role of the gut-brain axis in alcohol use disorders. The authors suggest that alcohol-induced gut dysbiosis contributes to neuroinflammation in the amygdala, which contributes directly to withdrawal behavior and symptoms (anxiety and depression). More evidence of the gut-brain axis will be summarized in subsequent sections.

Nutritional Deficiencies. By evaluating gastrointestinal function (assessed by d -xylose breath tests) investigators found that chronic alcohol overconsumption seems to cause malabsorption in the small intestine, comparable to patients with untreated celiac disease. It is likely that compromised gut function leads to reduced absorption of nutrients. Any damage to the liver can compromise the metabolism of micronutrients. Additionally, alcohol instead of food leads to poor nutritional intake, making it difficult to determine if nutrient deficiencies stem from primary malnutrition or secondary malnutrition, which occurs from alterations in the absorption, metabolism, utilization, and excretion of nutrients.

It is well established that thiamine deficiency is linked to alcoholism and can lead to Wernicke–Korsakoff syndrome. Mechanisms of thiamine deficiency include inadequate intake, decreased absorption from the gastrointestinal tract, hypomagnesaemia, and increased utilization in the cells. Intravenous thiamine is routinely administrated in hospital settings for AUD. Vitamin B6 may also be deficient due to increased utilization and reduced formation. Serum folic acid concentrations are often low in AUD and some authors have concluded that hyperhomocysteinemia is a probable cause. A recent study showed no differences in folate and vitamin B12 levels between individuals with alcohol dependence and social drinkers. Vitamin B12 deficiencies may be normal or elevated in the serum of AUD patients yet depressed in the liver due to decreased uptake by hepatocytes. Deficiencies of B6, folate, and B12 appear to be linked to ethanol-induced aberrant methionine metabolism yet supplementation with S-adenosylmethionine (SAM) for ALD has led to inconclusive results.

Both human and animal models have demonstrated adverse effects of alcohol on vitamin A metabolism. Low vitamin D levels have been associated with increased fractures in AUD. Links between iron and AUD appear inconclusive. In one investigation, the majority of patients with AUD did not display abnormal iron metabolism; some displayed deficiency while some exhibited iron overload. Micronutrient deficiencies appear inconsistent in human studies since they are retrospective and do not control for dietary intake. Because the prevalence of malnutrition in AUD is high, all patients should be screened for vitamin and mineral deficiencies through conventional laboratory testing and examination of clinical signs and symptoms. Generally, a complete multivitamin/mineral supplement is indicated to augment the diet upon cessation of alcohol, and IV thiamine may be warranted if Wernicke–Korsakoff syndrome is present.

Hormones. Research has shown that circulating leptin levels are increased in a dose-dependent manner in AUD, regardless of nutritional status or the presence of liver disease. These investigators found that leptin levels returned to normal after cessation of ethanol, while other investigators showed that leptin levels increase during the 10-day alcohol withdrawal period. Other research shows rises in leptin that eventually decrease between day 5 and 16, likely attributable to dietary changes (lipid intake). Gut-derived ghrelin appears to play a key role in alcohol-seeking behavior. Alcohol-dependent patients have increased ghrelin levels during early abstinence, increasing during the first week of alcohol withdrawal, whereas other research suggests that ghrelin drops and then rises between day 5 and 16. Similar to leptin, insulin appears to rise between day 2 and 5 and then decrease between day 5 and 16, but failure to adequately control for dietary intake make conclusions difficult to reach. In long-term abstinent alcoholics, investigators observed a significantly blunted response in blood glucose following a glucose infusion. Subjects exhibited trends toward both blunted responses in glucagon and insulin. Authors speculate that nervous system damage attributable to the effects of alcohol exposure is responsible for the insufficient hormonal response, particularly neurons in the hypothalamus. Taken together, the apparent link between alcohol abuse and abnormal hormonal responses highlights the negative impact of alcohol on the endocrine system, providing support for the need for dietary intervention in supporting long-term abstinence and recovery. Further links between hormones and addictive processes are discussed below.

Eating Behavior. Various studies have confirmed that AUD patients display abnormal preference for sweetened foods and beverages. Possible mechanisms for increased sweet preference include links between carbohydrates and serotonergic neurotransmission, the dopaminergic impact of sweetened foods, impaired hormonal responses to glucose, links between appetitive hormones and craving, and genetics. Tendencies to engage addiction-like eating patterns will be discussed in more detail in subsequent sections, as they cannot be ignored when attempting to improve nutritional habits in this population.

Nutritional Treatment. A recent meta-analysis concluded that nutritional interventions may have beneficial effects on clinical outcomes for patients with alcoholic hepatitis or cirrhosis, including survival and decreased risk of hepatic encephalopathy and infections. Medical interventions for alcoholic hepatitis have been described elsewhere and emerging evidence suggests potential benefit from microbiota-based treatments for ALD including fecal transplants and probiotics/prebiotics, as well as possibly additional polyphenolic compounds such as epigallocatechin gallate (EGCG). In a randomized controlled trial, hospitalized patients with alcoholic hepatitis received 7 days of oral supplementation with cultured Lactobacillus subtilus / Streptococcus faecium (1500 mg/day) and had significant restoration of bowel flora and reduction of LPS. Given what is known about the link between dietary fatty acids and inflammation, emphasis on omega-3 essential fatty acids should be considered an important part of nutrition therapy. In animal models, dietary flaxseed oil ameliorates ALD via anti-inflammation and modulating gut microbiota. In other rodent research, polyphenols from olive oil were protective against alcohol-induced oxidative stress. Nutraceutical regimens to ameliorate the toxic effects of alcohol merit further attention. Nutrition intervention strategies specifically for AUD are summarized in Table 2.1 . Overall recommendations common for all substance use disorders are summarized in Table 2.2 .

Stimulants

Cocaine. Similar to AUD, patients with a history of cocaine use disorder (CUD) have a higher preference for sucrose-sweetened beverages and a higher overall intake of carbohydrates. Cases of Wernicke's encephalopathy have been reported in crack-cocaine users who did not regularly consume alcohol, indicative of thiamine malnutrition. Cocaine-dependent men are more likely to skip breakfast than healthy men and to consume higher amounts of fatty foods, reflected by increased levels of monounsaturated and saturated fatty acids in plasma.

In one sample of nonopioid and nonalcohol-dependent persons with cocaine dependence, low polyunsaturated fatty acid (PUFA) levels measured 2 weeks after hospital admission served as a predictor of relapse after 3 months. Investigators suspect that since PUFAs can influence serotonergic and dopaminergic neurotransmission, altered reward mechanisms might influence drug-taking behavior. In a small sample, polysubstance abusers who received 3g omega-3 PUFAs daily for 3 months had significant decreases in measures of anxiety, persisting for at least 3 months post-treatment. While more data on the link between PUFAs and cocaine is needed, this may prove to be a beneficial nutritional strategy.

Cocaine-dependent men exhibit a trend toward lower circulating leptin levels. There is evidence that overeating patterns can precede the recovery process but the effect may be disguised by lack of weight gain. Authors suggest that chronic cocaine use directly interferes with metabolic processes resulting in an imbalance between fat intake and storage. Altered hormones combined with addiction-like eating is likely to explain excessive weight gain upon cessation of the drug. In a large US adult population study, cocaine use has been associated with elevated blood pressure.

In a small sample of HIV-infected drug users, cocaine users had a higher relative abundance of Bacteriodetes in their intestines, suggesting that the drug may contribute to changes in the microbiome. In animal models, alterations in the gut microbiota via antibiotic treatment enhanced behavioral response to cocaine, as modulated by reward circuitry in the brain. Other animal research has led investigators to propose that targeting the microbiota-gut-brain axis has promise in the treatment of co-occurring HIV and cocaine abuse. Taken together, cocaine use is associated with altered physiology in the gut, brain, and endocrine system.

While it is unclear if some of the observable alterations precede drug use, nutrition therapy designed to restore gut flora, stabilize hormones, and reduce addictive neuro-circuitry appears promising in the treatment of CUD. In one small study, supplemental N-Acetylcysteine (NAC) decreased cue-induced cravings in cocaine-dependent individuals. NAC stimulates cysteine-glutamate exchange and can restore glutathione (antioxidant) which appears to be linked to addiction signaling proteins and may have benefits for other substances as well. While rodent research has generated compelling findings, human studies are inconclusive. Additional research linking cocaine to NAC, overall nutritional status, and microbiome is needed.

Methamphetamine. Methamphetamine (MA) use is generally associated with decreased BMI. In rodents, acute administration of MA has led to significant reductions in the appetite hormone NP-Y consistent with humans who report lost hunger during MA use. There are published case reports of MA use for weight control in women with eating disorders and larger studies show associations with bulimia nervosa (BN), but not anorexia nervosa. There also exists evidence of hyperphagia and rebound weight gain in amphetamine-treated rodent models during the first month of abstinence. In one study from Australia, amphetamine users were nearly twice as likely to become obese than opioid users. Clinical anecdote suggests that rebound weight gain in humans during first months of abstinence can be as high as 10–30 lbs. per month for previously underweight patients, but eating behaviors and food preference during early recovery from MA has not been adequately described.

An intriguing link between MA and oral health exists. Anything that effects dental health has the potential to impact all areas of nutrition via influence on food choices. Several studies have linked IV MA use with dental problems including no visits to the dentist within past year. Other articles have suggested that dentists can play a crucial role in the early detection of MA use. It is unknown if the increase in dental disease is due to hygiene habits or from secondary effects of the drug, as dental problems have been linked with other illicit substances including cocaine. It is likely that high intake of sugar sweetened beverages and other sugar-laden foods contributes to this association, as well as increased acidity in the oral cavity. Animal data suggests that MA can cause altered carbohydrate metabolism and cause dysregulation of calcium and iron homeostasis. It is possible that altered calcium metabolism may be linked to MA-induced dental disease but more studies are needed to explore potential underlying mechanisms.

Research on MA-dependent humans in China showed that levels of total cholesterol, triglycerides, and glucose are significantly decreased on the second day of hospital admission, indicative of malnutrition. Consistent with findings of increased oxidative stress in polysubstance users, measures of MA-induced neurotoxicity are reduced by antioxidants selenium and CoQ10. Supplemental antioxidants appear promising, particularly if there are challenges implementing nutrition therapy focused on whole plant foods with high fiber and high antioxidant potential. Similar to alcohol and other intoxicating drugs, MA in high doses disrupts epithelial barrier function by modulating tight junction integrity and epithelial cell viability. To date, links between MA use and gut health have only been explored in animal models, but suggest that administration of the drug leads to dysbiosis. Specifically, propionate-producing genus Phascolarcobacterium was repressed by MA and the family Ruminococcaceae (linked to anxiety) was elevated. Investigations exploring links between MA and the microbiome are needed. Nutrition intervention strategies specifically for stimulants cocaine and MA are summarized in Table 2.3 . General recommendations for SUD are summarized in Table 2.2 .