Nutritional Deficiency and Alcohol Use Disorders (Slide 1)

 

Ann M. Manzardo, Ph.D.

 

Prepared for the Alcohol Medical Scholars Program

 

January, 2011

 

 

I.   Introduction (Slide 2: Image- tumor on thyroid gland/goiter)

            A.  Severe nutritional deficiencies once common, now rare in western countries1

                        1. Availability of food ↑ over time

                        2. Nationalized fortification of foods

                                    a. Begun in US early 1900’s

                                    b. Iodine added to salt (1924), prevent goiters

                                    c. Dairy products enriched (1940’s) (Slide 3: Image, bone softening due to rickets)

                                                1’ Calcium/Vitamin D to milk, prevent rickets

                                                2’ Vitamin A to margarine, prevent nightblindness

                                    d. Flour, bread, pasta & rice products enriched (1940’s)

                                                1’ Restored B vitamins lost in milling

                                                            a’ Niacin to prevent pellagra

                                                            b’ Thiamine to prevent beriberi

                                                            c’ Riboflavin to prevent ariboflavinosis

                                                2’ Folic acid added later (1998)

                                                            a’ Prevent neural tube defects (e.g., spina bifida)

                                                            b’ Reduce infant mortality

            B. Remains a problem for developing countries

                        1. Shortage of food

                        2. No fortification

                        3. Political problems with food distribution

            C. Who is at risk of nutritional deficiency in developed world today

                        1.  Generally high risk groups (Slide 4)

                                    a. Elderly

                                                1’ ↓ Attention to diet

                                                2’ Change in appetite

                                                3’ ↓ GI absorption with age

                                    b. Medical conditions

                                                1’ Excessive vomiting (e.g. cancer treatment, pregnancy)

                                                2’ Bowel dysfunction (e.g. celiac disease, gastric bypass surgery for obesity)

                                    c. Some psychiatric disorders

                                                1’ Dementias (Alzheimer’s), with poor self care

                                                2’ Eating disorders (e.g. anorexia nervosa)

                                                3’ Alcohol Use Disorders (AUDs) or heavy alcohol drinkers

            D. This lecture focuses on alcohol and nutrition (Slide 5)

                        1. Some definitions

                        2. How AUDs relate to nutritional deficiencies

                        3. Key role of thiamine

                        4. Consequences of thiamine deficiency in AUDs

                         5. Roles of other B vitamins in AUDs

                        6. How to help

II. Definitions

            A. Alcohol Abuse: 1+ recurrent in same 12 months (Slide 6)

                        1. ↓ Ability fulfill role obligation

                        2. Use in hazardous situations

                        3. Legal problems

                        4. Social or interpersonal problems

                        5. Never dependent

            B. Alcohol Dependence: 3 + recurrent in same 12 months

                        1. Tolerance (need more for effect)

                        2. Withdrawal

                        3. Use heavier or longer than intended

                        4. Desire or inability to cut down

                        5. Activities ↓ due to alcohol use

                        6.  ↑ Time spent on alcohol-related activities

                        7. Ongoing use despite consequences

            C. Definition of a micronutrient (Slide 7)

                        1. Needed in small amounts, (<100 μg/day)

                        2. “Essential” for metabolism/growth/development

                        3. 2 main kinds (vitamins/minerals)

                                    a. Definition of vitamin (Slide 8)

                                                1’ Organic compound

                                                2’ Necessary for bodily metabolism

                                                3’ Source

                                                            a’ Some synthesized

                                                            b’ Others only diet (eg, folate, pyridoxine)

                                    b. Definition of mineral

                                                1’ Chemical element (trace element)

                                                2’ Salt or ion

                                                3’ Necessary for growth/development

                                                4’ Diet only source

III. How AUDs relate to nutritional deficiencies2,3 (Slide9)

            A. Lifestyle ↑ risk (Slide 10)

                        1. Poor diet

                        2. ↓ access to food

                        3. Alcohol preferred to food

            B. Impaired absorption (Slide 11: Image of damaged gastric mucosa)

                                    a. Alc ↓ vit absorption

                                    b. Corrosive effects of alcohol on gut

                                    c. Physical barrier to distribution of nutrients3

                                                1’ Inflammation of the bowel (gastric mucosa)

                                                2’ Nutrients can’t cross inflamed cell membrane

            C. Selective depletion of B vitamins in AUD’s (Slide 12)

                        1. B vitamins water-soluble (rather than fat-soluble)

                                    a. ↓ storage in cells

                                    b. Levels ↓ quickly                             

                                    c. ↑ daily intake needed

                        2. These include B1- major focus of this lecture

IV. Vitamin B1 (thiamine) deficiency & AUDs (Slide 13)

            A. Major contributor to nutritional problems in AUDs3

                        1. Estimated >30% experience some deficiency

                        2. Symptoms may be absent/misdiagnosed

            B. Thiamine needed for sugar metabolism4
                        1. Main glucose metabolism (kreb cycle) (Slide 14)
                                    a. Uses oxygen to metabolize sugar
                                    b. Produces energy
                                    c. Alc ↑ sugar metabolism in kreb
                                    d. This ↑ thiamine use
                                    e. Thiamine deficiency produced
                        2. Alternate sugar metabolism is pentose phosphate (PP) shunt (Slide 15)
                                    a. Here transketolase enzyme is key
                                    b. Transketolase uses thiamine to work
                                    c. Low thiamine → PP path not work well

                                                1' ↓ DNA synthesis
                                                2' ↓ cell growth

                                    d. Vulnerability here is genetically influenced

                                                1’ ↓ transketolase, ↑ problems.

                                                2’ I'll return to this later

V. Consequences of thiamine deficiency in AUDs (Slide 16)

            A. Vulnerable cells damaged/destroyed4

                        1. Heart muscle/neurons most vulnerable

                        2. They have ↑ energy demand

                        3. Also have ↓ capacity for energy storage

            B. Clinical symptoms, 2 systems can be affected 3,5

                        1. Cardiovascular (wet beriberi)

Slide 17:          Image 1- normal vs enlarged heart

                        Image  2- thumbprint evidence of swelling (pitted edema)

 

                                    a. Shortness of breath

                                    b. Irregular heartbeat

                                    c. Edema

                                    d. Heart failure

                        2. Neurological (dry beriberi) (Slide 18: Images of neuropathy)

                                    a. Emotional disturbances (e.g. anxiety, depression)

                                    b. Pain/tingling/loss of feeling in limbs

                                    c. Muscle weakness in legs

                                    d. Balance/coordination problems

                        3. Beriberi reversible if found early

            C. Neurological syndromes (rare but serious)5 (Slide 19)

                        1. Wernicke’s encephalopathy (reversible)

Slide 20:          Animation1- paralysis of left eye when look to left

                        Photo- example of left eye paralysis

                        Animation 2- jerky eye movements side to side

                                    a. Sudden onset of symptoms

                                                1’ Impaired eye movement

                                                            a’ Can’t look to the side (opthalmoplegia)

                                                            b’ Jerky eye movements (nystagmus)

                                                2’ Staggering gate (ataxia)

                                    b.  Untreated can →

                                                1’ Korsakoff’s syndrome

                                                2’ Death

                        2. Korsakoff’s syndrome5 (Slide 21)

                                    a. Symptoms

                                                1’ Confusion

                                                2’ Severe memory loss (amnesia), 2 kinds

                                                            a’ Create new memories (anterograde)—this is key

                                                            b’ Recall past memories (retrograde)

                                                3’ Confabulation

                                                            a’ False memories/beliefs/”storytelling”

                                                            b’ Jumbling of actual events

                                                4’ ↓ communication skills/↓ interests (apathy)

                                                5’ Lack of “insight”(awareness) of disease

                                    b. Coma/death if untreated

                                    c. May require institutionalization/long term care                  

            D. Genetic vulnerability to thiamine deficiency6,7 (Slide 22)

                        1. Sub-population identified, ~10% frequency6

                                    a. Abnormal function of transketolase enzyme

                                                1’ ↓ affinity for thiamine

                                                2’ ↑ thiamine needed to activate                                                 

                                    b. ↑ alcohol-related problems

                                                1’ ~30% of AUDs with Wernicke-Korsakoff Syndrome6

                                                2’ Neurological damage, normal thiamine levels

                                    c. Both males & females                                

                        2. Source of defect unknown

                                    a. Autosomal recessive inheritance

                                    b. No gene identified

                        3. More common in AUD families7

VI. Examples similar problems with other B vitamins (Slide 23)

            A. Part of general B vit deficiency in AUD, described above (Slide 24)

            B. Folate (vitamin B9)

                        1. >40% AUDs deficient

                        2. Function

                                    a. Synthesis of DNA/RNA

                                    b. Needed to make red blood cells (RBCs)

                        3. Symptoms of deficiency (Slide 25: Image of megoblastic RBCs)

                                    a. ↓ RBCs, anemia (2 kinds)

                                                1’ Abnormally large RBCs (megaloblastic anemia)

                                                2’ ↑ RBC loss (hemolytic anemia)

                                    b. ↓ appetite

                                    c. Weakness, fatigue

                                    d. Hair loss

                        4. Symptoms generally reversible

            C. Pyridoxine (vitamin B6)

                        1. Up to 50% prevalence in AUDs

                        2. Broad range of vitamin functions include

                                    a. Metabolism proteins/sugars/fats

                                                1’ Energy production in cell

                                                2’ Cell growth  

                                    b. Production of RBCs

                                    c. Synthesis of neurotransmitters (dopamine, serotonin)

                                    d. Activation of other vitamins (eg, niacin)

                        3. Symptoms of deficiency, similar to niacin deficiency (pellagra)

                                    a. Anemia (sideroblastic anemia) (Slide 26: Image- iron trapped in RBC membranes)

                                                1’ Can’t process iron to make hemoglobin

                                                2’ ↓ healthy RBCs

                                                3’ ↑ abnormal/immature RBCs (sideroblasts)

                                    b. Skin inflammation (dermatitis), lips (cheilosis)

Slide 27           Image 1- facial dermatitis

                        Image 2- angluar cheilosis around mouth

                                    c. Nerve problems/damage (may be permanent)

                                                1’ Numbness/tingling in hands/feet

                                                2’ Neuropathy

                                    d. Behavior (confusion, somnolence)

            D. Riboflavin (vitamin B2)

                        1. ~17% deficient in AUD (ariboflavinosis)

                        2. Function

                                    a. Involved in transfer of electrons (electron transport chain)

                                                1’ Metabolism of sugars

                                                2’ Energy production in cell

                                    b. Synthesis of glutathione (antioxidant molecule)

                        3. Symptoms of deficiency, skin/mucus membranes

                                    a. Inflammation mouth/tongue (cheilosis) (Slide 28: Image mouth ulcers)

                                                1’ Mouth ulcers

                                                2’ Cracked lips

                                                3’ Inflamed corners of mouth (angular cheilosis)

                                    b. Inflammation of eyes

                                                1’ Bloodshot

                                                2’ Itchy/watery

                                                3’↑ Sensitivity to light

                                    c. Dermatitis (Slide 29: Image of facial Seborrheic Dermatitis)

                                                1’ Scaly, oily rash

                                                2’ Face (upper lip), genitals

                                    d. Most symptoms reversible (scarring/nerve damage may persist)

VI. Clinical care for nutritional deficiency2 (Slide 30)

            A. Laboratory measures of nutritional status

                        1. Blood levels

                                    a. Rarely tested in AUDs2

                                    b. Costly/considered unnecessary

                        2. Supplementation is standard of care

            B. Treatments & interventions for nutritional deficiency2

                        1. Supp guidelines for AUDs (Slide 31)

                                    a. B-complex vitamins, 7-14 days

                                                1’ Full complex recommended

                                                2’Includes 8 vitamins (Slide 32)

                                                            a’ B1 (thiamine), 100 mg

                                                            b’ B2 (riboflavin), 1.3 mg

                                                            c’ B3 (niacin), 10-50 mg

                                                            d’ B5 (pantothenic acid), 10 mg

                                                            e” B6 (pyroxidine), 1-3 mg

                                                            f” B7 (biotin), 300 mcg

                                                            g” B9 (folate), 1 mg

                                                            h” B12 (cobalamin), 6-12 mg

                                                3’ Oral, daily use recommended                                            

                                    b. Comprehensive multivitamins prescribed

                                                1’ Must include 100 mg thiamine & 1 mg folate

                                                2’ Should include minerals

                                                            a’ Help vitamins work

                                                            b’ Mineral deficiency slows recovery

                                                            c’ Recommended daily intake (USDA)

                                                3’ Prenatal vitamins used, inexpensive/easy

                        2. Acute thiamine deficiency2

                                    a. Treatment of Wernicke-Korsakoff syndrome (Slide 33)

                                                1’ Hospitalization advised

                                                            a’ Intravenous thiamine, 100 mg

                                                            b’ 1-2 x daily

                                                            c’ 3-5 days

                                                            d’ Include B complex

                                                2’ Improvements expected 1-2 days, but could take months.

                                                 3’ If severe, may never recover (~30%)

                        3. Limitations of these treatments4

                                    a. ↓ Bioavailability water-soluble B vitamins

                                    b. Gastric/metabolic problems

                                    c. Long-term treatment needed

                                    d. Primary drinking problem must be addressed

                         4. Alternative sources of thiamine8

                                    a. Lipid soluble analogues available which (Slide 34)

                                                1’ ↑ thiamine in AUDs (better than water-soluble thiamine)

                                                2’ ↑ transketolase in AUDs

                                                3’ Long-term effect

                                    b. Analogues (2 available)8

                                                1’Allithiamine, natural compound, in onion/garlic

                                                2’Benfotiamine, synthetic compound

                                                            a’ 150 mg/day effective in AUDs

                                                            b’ Appears safe

                                                            c’ Reverses neuropathy in AUDs/diabetes

                                                            d’ Over-the-counter, most countries

            C. AUD treatment

                        1. Brief intervention (for hazardous use not abuse or dependence) (Slide 35)

                                    a. 15 minute initial contact (5 A’s of SBIRT)

                                                1’ Assess using a screening tool

                                                2’ Advise to quit or reduce to healthy standard

                                                3’ Agree on goals for reducing use

                                                4’ Assist in motivation change

                                                5’ Arrange follow-up or referral

                                    b. At least 1 follow-up

                                    c. Reduce average # drinks/week by ~25%

                                    d. Refer to Moderation Management

                                                1’ Mutual help group modeled on Alcoholics Anonymous

                                                2’ Goal is moderation in consumption, not abstinence

                        2. If abuse or dependence (Slide 36)

                                    a. 12-step mutual help groups (Alcoholics Anonymous)

                                    b. Referral to higher level of AUD care

                                                1’ Day treatment

                                                2’ Residential

                                                3’ Clean & sober living environment

                                    c. Consider medications

                        3. Medications for AUDs (Slide 37)

                                    a. Include psychosocial intervention

                                    b. Naltrexone (Revia) 50-150 mg daily

                                                1’ Opiod Blocker

                                                2’ Believed to reduce craving

                                    c. Acamprosate (Campral) ~2 g daily

                                                1’ Antagonist to NMDA-glutamate receptor

                                                2’ May decrease time to relapse

                                    d.Disulfiram (Antabuse)250 mg daily

                                                1’ Blocks ALDH causes nausea/vomiting if drink alcohol

                                                2’ Deterrent; issues with compliance

                                                3’ Cannot use in ALD, diabetes, heart disease

VII Summary 

            A. Topics reviewed (Slide 38)

                        1. Reasons nutritional deficiencies are found with AUDs

                        2. What kinds of deficiencies are problems in AUDs

                        3. Effects of nutritional deficiency on health in AUDs

                        4. How to help

            B. Take-home message

                        1. Nutritional deficiency a major risk for people with AUD’s

                        2. Major health problems due to B vitamin deficiency, particularly thiamine

                        3. Principle targets heart muscle and neurons

                        4. Treatment of primary AUD most effective means to improve outcome

 

References:

 

1. The History and Future of Food Fortification in the United States: A Public Health Perspective, Backstrand JR, (2002) Nutrition Reviews, Jan;60(1): 15-26

 

2. Oral Nutritional Supplementation for the Alcoholic Patient: a Brief Overview, Markowitz JS, McRae AL, Sonne SC. (2000)  Ann Clin Psychiatry Sep;12(3):153-8

 

3. Mechanisms of Vitamin Deficiency in Chronic Alcohol Misusers and the Development of the Wernicke-Korsakoff Syndrome, Thomson AD, (2000)Alcohol Alcohol Suppl.,May-Jun;35(1):2-7

 

4. The role of thiamine deficiency in alcoholic brain disease, Martin PR, Singleton CK, Hiller-Sturmhöfel S., (2003)Alcohol Res Health 27(2):134-42

 

5. The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment, Kopelman MD, Thomson AD, Guerrini I, Marshall EJ, (2009) Alcohol & Alcoholism 44(2):148-154

 

6. Individual susceptibility to Wernicke-Korsakoff syndrome and alcoholism-induced cognitive deficit: impaired thiamine utilization found in alcoholics and alcohol abusers. Heap LC, Pratt OE, Ward RJ, Waller S, Thomson AD, Shaw GK, Peters TJ. (2002) Psychiatr Genet 12(4):217-24.

 

7. Transketolase Abnormality in Cultured Fibroblasts from Familial Chronic Alcoholic Men and Their Male Offspring, Mukherjee AB, Svoronos S, Ghazanfari A, Martin PR, Fisher A, Roecklein B, Rodbard D, Staton R, Behar D, Berg CJ, Manjunath R, (1987) The Journal of Clinical Investigation, Inc. April;79:1039-1043

 

8. Pharmacokinetics of thiamine derivatives especially of benfotiamine, Loew D, (1996) Int J Clin Pharmacol Ther  Feb;34(2):47-50