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Causes of High Homocysteine Levels (Hyperhomocysteinemia) Many factors contribute to high homocysteine levels: Insufficient folate, vitamin B 6 , vitamin B 12 , betaine, vitamin B 2 , and magnesium Certain prescription drugs (including cholestyramine, colestipol, fenofibrate, levodopa, metformin, methotrexate, high-dose niacin, nitrous oxide, pemetrexed, phenytoin, sulfasalazine) High-methionine diet (including red meat and dairy products) Smoking High coffee consumption Alcohol consumption Advancing age Obesity Genetic variant that causes an impaired ability to metabolize active folate from folic acid Note: Life Extension believes that the optimal range for homocysteine levels is 11 µmol/L) has been associated with a substantial increase in risk of dementia in the elderly

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Screening for alternate antibodies in instances where autoantibodies associated with the conventional disease are absent is essential to understand the underlying mechanisms behind these irAEs for further management